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Modulation of Akt kinase activity by ubiquitination

Research Project

Project/Area Number 22370046
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionHokkaido University

Principal Investigator

NOGUCHI Masayuki  北海道大学, 遺伝子病制御研究所, 教授 (40359477)

Co-Investigator(Kenkyū-buntansha) SUIDU Futoshi  北海道大学, 遺伝子病制御研究所, 講師 (90431379)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2011: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
KeywordsAKT / 蛋白分解 / NS1 / TCL1b / シグナル伝達 / Akt
Research Abstract

Serine threonine Akt is a core intra-cellular survival regulator. In this study, we demonstrated that the functional interaction of NS1 with Akt and clarified that the functional importance of influenza virus NS1 with Akt in biocmical analysis. The results together supported the functional importance of influenza virus NS1 with Akt.We clarified that TCL1b functions as an Akt kinase co-activator and exhibitsoncogenicity both in vitro and in vivo using biochemical analysis, bioinformatics, and generation of TCL1b transgenic mice which resulted in angiosarcoma. By immunohistochemistry, most of human angiosarcoma samples and various cancer tissues were positively stained by both anti-TCL1b and anti-phospho-Akt antibodies. Moreover,TCL1b structure-based inhibitor “TCL1b-Akt-in” inhibited Akt kinase activity, hence, suppressed cellular proliferation of sarcoma. The current study disclosed TCL1b bears oncogenicity, and hence serves as a novel therapeutic target for human neoplasticdiseases.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (43 results)

All 2012 2011 2010

All Journal Article (7 results) (of which Peer Reviewed: 5 results) Presentation (34 results) Book (2 results)

  • [Journal Article] IL-10産生T細胞を誘導する樹状細胞2012

    • Author(s)
      平田徳幸
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 57(3) Pages: 259-263

    • Related Report
      2012 Annual Research Report
  • [Journal Article] The role of tumor necrosis factor-α for interleukin-10 production by murine dendritic cells2011

    • Author(s)
      N. Hirata, H.ogura, M.Satoh, M Noguchi, M.Matumoto,H.Togashi,K.Onoe,K.Iwabuc hi,Y.Yanagawa
    • Journal Title

      Cell Immunol

      Volume: 266 Pages: 165-171

    • NAID

      120002893812

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of tumor necrosis factor- for interleukin-10 production by murine dendritic cells.2011

    • Author(s)
      N. Hirata
    • Journal Title

      Cell Immunol

      Volume: 266 Pages: 165-171

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Akt by phosphorylation of distinct threonine and serine residues Threonine:Structure, Biosynthesis and Functions2011

    • Author(s)
      M. Noguchi & F. Suizu
    • Journal Title

      Advances in Medicine and Biology

      Volume: 47 Pages: 139-162

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Characterization of the interaction of Influenza virus NS1 with Akt2010

    • Author(s)
      M. Matsuda, F.Suizu,N.Hirata ,T.Miyazaki,C.Obuse,M.Noguc hi
    • Journal Title

      Biochem Biophys Res Communic

      Volume: 395 Pages: 312-317

    • NAID

      120002191111

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dendritic cell-derived TNF-αisresponsible for development of IL-10- producing CD4+ T cells2010

    • Author(s)
      N.Hirata,Y.Yanagawa,M.Satoh,H.Ogura,T.Ebihara,M.Noguchi,M.Matsumoto,H.To gashi,T.Seya, K.Onoe,K.Iwabuchi
    • Journal Title

      Cell Immunol.

      Volume: 261 Pages: 37-4

    • NAID

      120001875433

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dendritic cell-derived TNF-・is responsible for development of IL-10-producing2010

    • Author(s)
      N.Hirata
    • Journal Title

      Cell Immunol

      Volume: 261 Pages: 37-41

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] ウィルス感染症におけるTCL1BによるAKTシグナル伝達系の活性化機構2012

    • Author(s)
      野口昌幸
    • Organizer
      第86回日本感染症学会
    • Place of Presentation
      長崎市・長崎ブリックホール
    • Year and Date
      2012-04-25
    • Related Report
      2012 Final Research Report
  • [Presentation] Protooncogene TCL1b functions as an AKT kinase co-activator that exhibitsoncogenic potency in vivo2012

    • Author(s)
      M. Hashimoto, M. Matsuda F. Suizu,T.Nagamine,N. Hirata,H. Noguchi,S. Tanaka,W. Tokuyama,M. Noguchi
    • Organizer
      第71回日本癌学会学術集会
    • Place of Presentation
      札幌市・札幌コンベンションセンター
    • Related Report
      2012 Final Research Report
  • [Presentation] Modulation of the Akt signal by its binding proteins.2012

    • Author(s)
      野口昌幸、水津太
    • Organizer
      第35回分子生物学会
    • Place of Presentation
      福岡市・福岡国際会議場
    • Related Report
      2012 Final Research Report
  • [Presentation] Protooncogene TCL1b Functions as An Akt Kinase Co-activator that Exhibits On cogenic Potency In Vivo.2012

    • Author(s)
      M Hashimoto,F Suizu,W Tokuyama,H Noguchi,M Matsuda,N Hirata,T Nagamine,S Tanaka,M Noguchi
    • Organizer
      第35回分子生物学会
    • Place of Presentation
      福岡市・福岡国際会議場
    • Related Report
      2012 Final Research Report
  • [Presentation] ウイルス感染症におけるTCL1BによるAKTシグナル伝達系の活性化機構2012

    • Author(s)
      野口 昌幸
    • Organizer
      第86回日本感染症学会
    • Place of Presentation
      長崎ブリックホール(長崎県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] PROTOONCOGENE TCL1B FUNCTIONS AS AN AKT KINASECOACTIVATOR THAT EXHIBITS ONCOGENIC POTENCY IN VIVO.2012

    • Author(s)
      橋本 学
    • Organizer
      MECHANISMS & MODELS OF CANCER
    • Place of Presentation
      Cold Spring Harbor Laboratory(アメリカ)
    • Related Report
      2012 Annual Research Report
  • [Presentation] プロトオンコジーンTCL1bはAkt活性化補助因子であり、in vivoでの腫瘍化を示す2012

    • Author(s)
      橋本 学
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Akt結合因子による細胞反応性の修飾の分子機構2012

    • Author(s)
      野口 昌幸
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Protooncogene TCL1b Functions as An Akt Kinase Co-activator that Exhibits On cogenic Potency In Vivo.2012

    • Author(s)
      橋本 学
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Characterization of the interaction of Akt with virus NS12011

    • Author(s)
      M.Matsuda
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Keystone Resort (USA)
    • Year and Date
      2011-02-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Characterization of the interaction of Akt with virus NS12011

    • Author(s)
      M. Matsuda, Suizu F, Hirata N, Miyazaki T, Obuse C, Noguchi M
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Keystone Resort(コロラド・米)
    • Related Report
      2012 Final Research Report
  • [Presentation] Characterization of protooncogene TCL1b as an Akt kinase co-activator2011

    • Author(s)
      M. Hashimoto,F. Suizu,W. Tokuyama,H.Noguchi,M. Matsuda,N. Hirata,T. Nagamine,S. Tanaka, M .Noguchi
    • Organizer
      CSHL Meeting
    • Place of Presentation
      Cold Spring HarborLaboratory(ニューヨーク・米)
    • Related Report
      2012 Final Research Report
  • [Presentation] Characterization of the interaction ofinfluenza virus NS1 with Akt2011

    • Author(s)
      M. Matsuda,F. Suizu,N. Hirata,T.Miyazaki,C. Obuse, M.Noguchi
    • Organizer
      国際微生物学連合2011会議
    • Place of Presentation
      札幌市・札幌コンベンションセンター
    • Related Report
      2012 Final Research Report
  • [Presentation] インフルエンザウイルス感染症における感染宿主細胞のAKTとインフルエンザNS1蛋白結合の機能的解析2011

    • Author(s)
      野口昌幸
    • Organizer
      第85回日本感染症学会総会
    • Place of Presentation
      東京・ザ・プリンスパークタワー東京
    • Related Report
      2012 Final Research Report
  • [Presentation] Characterization of the interaction of influenza virus NS1 with Akt2011

    • Author(s)
      M. Matsuda,F. Suizu,N. Hirata,T. Miyazaki,C. Obuse, M.Noguchi
    • Organizer
      国際微生物学連合2011会議
    • Place of Presentation
      札幌市・札幌コンベンションセンター
    • Related Report
      2012 Final Research Report
  • [Presentation] プロトオンコジーンTCL1bの生物機能解析2011

    • Author(s)
      M.Hashimoto, F.Suizu, M.Matsuda, N.Hirata, M.Noguchi
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋市・名古屋国際会議場
    • Related Report
      2012 Final Research Report
  • [Presentation] TNF-α drives IL-10 production inmurine dendritic cells2011

    • Author(s)
      Hirata,Y.Yanagawa ,K.Iwabuchi ,M.Sato,H.Ogura,K.Onoe ,M.Noguchi
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉市(幕張メッセ)
    • Related Report
      2012 Final Research Report
  • [Presentation] プロトオンコジンTCL1 bのAKT活性化補助因子としての役割について2011

    • Author(s)
      M.Hashimoto, F. Suizu,M. Matsuda, N. Hirata, M. Noguchi
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜市・パシフィコ横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] Characterization of protooncogene TCL 1b as an Akt kinase co-activator.2011

    • Author(s)
      M.Noguchi
    • Organizer
      CSHL Meeting
    • Place of Presentation
      Cold Spring Harbor Laboratory(アメリカ)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Characterization of the interaction of influenza virus NS1 with Akt.2011

    • Author(s)
      M. Matsuda
    • Organizer
      国際微生物学連合2011会議
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Related Report
      2011 Annual Research Report
  • [Presentation] インフルエンザウイルス感染症における感染宿主細胞のAKT とインフルエンザNS1 蛋白結合の機能的解析2011

    • Author(s)
      野口 昌幸
    • Organizer
      第85回日本感染症学会
    • Place of Presentation
      ザ・プリンス パークタワー東京(東京都)
    • Related Report
      2011 Annual Research Report
  • [Presentation] プロトオンコジーンTCL1bの生物機能解析2011

    • Author(s)
      橋本 学
    • Organizer
      第70回日本癌学会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] TNF-α drives IL-10 production in murine dendritic cells.2011

    • Author(s)
      平田 徳幸
    • Organizer
      第40回日本免疫学会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] プロトオンコジンTCL1bのAKT活性化補助因子としての役割について2011

    • Author(s)
      橋本 学
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] TTCによるAkt活性調節機構の解析2010

    • Author(s)
      水津太
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] ユビキチン化によるAKT活性の調節メカニズムの解析2010

    • Author(s)
      水津太
    • Organizer
      第33回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Characterization of the interaction of influenza virus NS1 with Akt2010

    • Author(s)
      松田真実
    • Organizer
      第33回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド(兵庫県)
    • Year and Date
      2010-12-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] ユビキチン化によるAKTの活性化制御の仕組み2010

    • Author(s)
      野口昌幸
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2010-09-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] The role of dendritic cell-produced TNF-α in generation of IL-10-producingCD4+T cells2010

    • Author(s)
      Hirata,Y.Yanagawa,K.Iwabuchi,M.Satoh, H.Ogura,T.Seya,K.Onoe,M.Noguchi
    • Organizer
      14TH INTERNATIONAL CONGRESS OF IMMUNOLOGY,Kobe,Japan
    • Place of Presentation
      神戸市・神戸国際展示場
    • Year and Date
      2010-08-24
    • Related Report
      2012 Final Research Report
  • [Presentation] The role of dendritic cell-produced TNF-α in generation of IL-10-producing2010

    • Author(s)
      Hirata, N
    • Organizer
      14TH INTERNATIONAL CONGRESS OF IMMUNOLOGY
    • Place of Presentation
      神戸国際展示場(兵庫県)
    • Year and Date
      2010-08-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] ユビキチン化によるAKTの活性化制御の仕組み2010

    • Author(s)
      野口昌幸
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪市・大阪国際会議場
    • Related Report
      2012 Final Research Report
  • [Presentation] TTCによるAkt活性調節機構の解析2010

    • Author(s)
      水津太
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪市・大阪国際会議場
    • Related Report
      2012 Final Research Report
  • [Presentation] ユビキチン化によるAKT活性の調節メカニズムの解析2010

    • Author(s)
      F. Suizu,Y. Hiramuki,F. Okumura,M. Matsuda,A. Okumura,N. Hirata,M. Narita,T. Kohono,J. Yokota,M. Bohgaki,C. Obuse,S. Hatakeyama T. Obata,M Noguchi
    • Organizer
      第33回日本分子生物学会
    • Place of Presentation
      神戸市・神戸ポートアイランド
    • Related Report
      2012 Final Research Report
  • [Presentation] Characterization of the interaction of influenza virus NS1 with Akt2010

    • Author(s)
      M. Matsuda, F. Suizu, N. Hirata,T. Miyazaki,C. Obuse,M. Noguchi
    • Organizer
      第33回日本分子生物学会
    • Place of Presentation
      神戸市・神戸ポートアイランド
    • Related Report
      2012 Final Research Report
  • [Book] Regulation of Akt by phosphorylation of distinct threonine and serine residues Threonine:Structure Biosynthesis and Functions; Advances in Medicine and Biology2011

    • Author(s)
      M. Noguchi & F. Suizu.
    • Publisher
      Nova Science Publishers, New York. USA
    • Related Report
      2012 Final Research Report
  • [Book] Regulation of Akt by phosphorylation of distinct threonine and serine residues Threonine : Structure, Biosynthesis and Functions ; Advances in Medicine and Biology2011

    • Author(s)
      M.Noguchi, F.Suizu
    • Publisher
      Nova Science Publishers
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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